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CIM-REPARTI Seminar

Challenges in measuring Cardiac Function and dysfunction: A clinical perspective

Pierre Jordaan
Novartis Pharma
Basel
,
Switzerland

December 2, 2015 at
4:00 PMMcConnell Engineering Room 437

Nature has provided man with robust physiological systems to sustain life and ensure survival under adverse conditions. The cardiovascular system is such a system, with considerable redundancy to ensure a continuous blood circulation to the vital organs. Therefore, despite significant advances in medical research, the early identification of cardiotoxicity, which would allow early intervention, remains challenging.

Echocardiography and magnetic imaging are the two cornerstones of measuring cardiac function directly. Neither is optimal – technical issues including operator dependency causes considerable variability with echo’s (up to 12%), and accessibility, exposure to radiation and cost limit the routine use of MRI.

Cardiotoxicity can be either reversible or transient (Type I), or permanent (Type 2 ). Often dysfunction starts as functional changes and as the disease progresses, structural damage follows. However, non-specific cytotoxic agents may cause permanent damage to the heart and other organs that may only manifest and be diagnosed late.

Routine assessment for the early identification of cardiotoxicity in clinical research include circulatory biomarkers. Typically this includes the cardiac troponins (or CK/CK-MB) that measures myocardial cellular toxicity, and the natriuretic peptides, that reflect cardiac overload. More recently, disease-specific miRNA is being assessed, although it is still not clear if the miRNA elevation is pathology- or compound-specific or compound-agnostic, and whether they are epiphenomena or are actively involved in the pathologic process. What is clear that these circulatory biomarkers may occur transiently, and too early or too late blood sampling may not be diagnostic, despite the presence of structural disease.

Cardiotoxicity is especially relevant in oncology: As patients with cancer survive longer, cardiotoxicity may manifest after a long time. Secondly, targeted cancer therapy may alter the very core of life-sustaining pathways both in cancer cells and in healthy tissue, including the heart. Earlier identification of cardiac disfunction would potentially guide drug selection, trigger dose reduction, or alert the clinician to the need for preventative treatment, which has been effective in breast cancer, for example.